This F&S Core will provide CEG members with the ability to develop transgenic mice and to bred the mice under close maintenance in a pathogen-free environment. The Core consists of facilities and personnel for: 1) making gain-of- function transgenic mice in which DNA is micro- injected into fertilized mouse eggs; 2) developing transgenic mice derived from gene-targeted embryonic stem cells in which a function is lost (knockout); and 3) carrying out selected breeding to generate desired combinations of genetic alteration or to modify the genetic background of transgenic mice for experimental use. Dr. John Duffy is the director of this F&S Core. The personnel responsible for the construction of gain-of-function mice and of KO mice is Jonathan Neumann and john Duffy, respectively. Dr. Tom Doetschman, a well known expert in the transgenic and gene knockout field who was instrumental in establishing this core, will continue to provide new ideas and approaches to the facility. Consultation will be provided to Center investigators free of charge. Technical services for construction and breeding of gain-of-function and kO mice will be provided on a fee-for-service basis paid for by funds allocated to this core. Gain-of-function mice will be produced at a cost of $2,500/construct, while production of KO mouse line will be at a cost of $9,500, this includes gene targeting in ES cell ($4,300) and microinjection of E cells to produce gene targeted mice ($5,200). Costs for mouse breeding will be $2,275. Center investigators will first consult with J. Duffy an J Neumann to discuss their proposals for the generation of specific mice. If it is deemed a feasible project in these discussions, the investigators will consult with J. Duffy and J. Neumann on the construction of targeting vectors and the molecular biological aspects of the project. At this point, the Center investigators, J. Duffy, J. Neumann, and the Center Internal Advisory Board will meet to discuss the relevance for the proposed construction of the transgenic mice to the mission of the Center. It will be decided whether funds set aside for the generation of transgenic mice in the Center budget will be released to the Core to support the generation of the mice proposed.